High density porous materials

ABSTRACT

Porous materials are disclosed having densities of at least about 6 pounds per cubic foot (96.1 kg/m 3 ). The materials comprise silica and/or alumina.  
     The porous materials are useful as supports for binding various chemical and biological molecules. The materials are useful as supports for analytical processes such as ELISA, blotting, and hybridization assays. The materials can be used as reinforcement agents for organic, inorganic, or metallic materials.

FIELD OF THE INVENTION

[0001] The invention relates to porous materials and, more specifically,to porous silica materials. The materials are useful for the binding ofchemical and biological molecules to be used in various analyticalmethods.

BACKGROUND OF THE INVENTION

[0002] Various plastic, glass, and membrane materials have historicallybeen used to bind chemical and biological molecules for use in variousanalytic methods such as ELISA, Western blotting, and hybridizations.

[0003] These materials are limited by their relatively low loadingpotential, and by their non-porous nature.

[0004] U.S. Pat. No. 5,951,295 (issued Sep. 14, 1999) describes ceramicfused fiber enhanced dental materials, and methods for theirpreparation. Fused-fibrous material was taught comprising from about 1%to about 50% by weight alumina, from about 50% to about 98% silica, andfrom about 1% to about 5% by weight boron.

[0005] U.S. Pat. No. 5,964,745 (issued Oct. 12, 1999) describes animplantable system for bone or vascular tissue. The system comprisesporous linked fibrous biomaterial manufactured from nonwoven,randomly-oriented fibers linked together using a fusion source at aplurality of cross-points into a porous structure, said biomaterialhaving a plurality of voids of a predetermined mean void size effectivefor stimulating angiogenesis in said biomaterial from the tissue orbone.

[0006] U.S. Pat. No. 5,621,035 (issued Apr. 15, 1997) describes fillercompositions and ceramic enhanced dental materials. The preferredembodiment of the filler composition and the ceramic dental restorativematerial is comprised of about 22% by weight alumina, about 78% byweight silica, about 2% by weight silicon carbide, and about 2.85% byweight boron nitride with less than 1% cristobalite contamination.

[0007] Porous materials have been suggested by Yasukawa et al. (U.S.Pat. Nos. 5,629,186 and 5,780,281). A composite was prepared from silicaand/or alumina fibers with added boron nitride. The composites weresuggested as being useful for cell cultures, implants, andchromatography matrices.

[0008] There exists a need for materials which bind chemical andbiological molecules while having improved surface properties.

SUMMARY OF THE INVENTION

[0009] Porous materials suitable for the binding of chemical andbiological molecules are disclosed. The three dimensional properties ofthe materials results in improved loading properties. The materials canbe used in a wide array of chemical and biological assays to improvesensitivities.

DETAILED DESCRIPTION OF THE INVENTION

[0010] Porous materials

[0011] A preferred embodiment of the invention is directed towardsporous materials having densities of about 6 pounds per cubic foot (96.1kg/m³) and higher, about 8 pounds per cubic foot (128 kg/m³) and higher,about 12 pounds per cubic foot (192 kg/m³) and higher, about 24 poundsper cubic foot (384 kg/m³) and higher, about 36 pounds per cubic foot(577 kg/m³) and higher, about 48 pounds per cubic foot (769 kg/m³) andhigher, or about 64 pounds per cubic foot (1025 kg/m³) and higher. Thematerials can comprise up to about 100% silica, or up to about 60%alumina. The silica can be up to about 50% cristobalite, up to about 75%cristobalite, up to about 90% cristobalite, up to about 95%cristobalite, up to about 99% cristobalite, or can be about 100%cristobalite. The alumina can be aluminum borosilicate.

[0012] The exposed surface of the materials (“surface chemistry”) can beat least about 50% silicon dioxide, at least about 75% silicon dioxide,at least about 90% silicon dioxide, at least about 95% silicon dioxide,at least about 99% silicon dioxide, or can be about 100% silicondioxide.

[0013] The materials can comprise other metal oxides in addition to orin place of the silica. For example, tantalum oxide or zirconium oxidecan be incorporated into the materials.

[0014] The mean pore diameter of the materials can be less than 0.01microns, about 0.1 micron to about 5 microns, up to about 10 microns, upto about 20 microns, up to about 30 microns, up to about 40 microns, upto about 50 microns, up to about 100 microns, up to about 200 microns,up to about 300 microns, up to about 400 microns, up to about 500microns, or up to about 600 microns. Ranges of pore diameter includeabout 0.1 microns to about 1 micron, about 5 microns to about 10microns, about 20 microns to about 50 microns, about 100 to about 400microns, or about 200 microns to about 600 microns.

[0015] The surface properties of the materials can be modified bychemical reactions. Examples include modifying the hydrophobicity orhydrophilicity of the porous materials, and hydroxylation withphosphoric acid.

[0016] The materials can be reinforced using an additional silica gelThe materials can further comprise carbon fiber, organic fiberscontaining carbon, or other polymer materials.

[0017] Preparation of porous materials

[0018] The preparation of porous materials is generally described inU.S. Pat. No. 5,951,295 (issued Sep. 14, 1999).

[0019] Porous materials can be prepared from: (1) from about 1% to about50% by weight alumina; (2) from about 50% to about 98% by weight silica;and (3) from about 1% to about 5% by weight boron. In addition, thecomposition can further comprise silicon carbide up to about 3% byweight. The materials can comprise over 99% silica.

[0020] Generally, the process for preparing the porous materials cancomprise the following steps (as described in U.S. Pat. No. 5,951,295):

[0021] (1) preparation of a slurry mixture comprised of pre-measuredamounts of purified fibers/materials and deionized water;

[0022] (2) removal of shot from slurry mixture;

[0023] (3) removal of water after thorough mixing to form a soft billet;

[0024] (4) addition of a ceramic binder after the formation of thebillet;

[0025] (5) placement of the billet in a drying microwave oven formoisture removal; and

[0026] (6) sintering the dry billet in a large furnace at about 1600° F.or above.

[0027] The high purity silica fibers above are first washed anddispersed in hydrochloric acid and/or deionized water or other solvents.The ratio of washing solution to fiber is between 30 to 150 parts liquid(pH 3 to 4) to 1 part fiber. Washing for 2 to 4 hours generally removesthe surface chemical contamination and non-fibrous material (shot) whichcontributes to silica fiber devitrification. After washing, the fibersare rinsed 3 times at approximately the same liquid to fiber ratio for10 to 15 minutes with deionized water. The pH is then about 6. Excesswater is drained off leaving a ratio of 5 to 10 parts water to 1 partfiber. During this wash and all following procedures, great care must betaken to avoid contaminating the silica fibers. The use of polyethyleneor stainless steel utensils and deionized water aids in avoiding suchcontamination. The washing procedure has little effect on the bulkchemical composition of the fiber. Its major function is theconditioning and dispersing of the silica fibers.

[0028] The alumina fibers are prepared by dispersing them in deionizedwater. They can be dispersed by mixing 10 to 40 parts water with 1 partfiber in a V-blender for 21/2 to 5 minutes. The time required is afunction of the fiber length and diameter. In general, the larger thefiber, the more time required.

[0029] Generally, in order to manufacture low density porous materials,for example, densities below 12 lb/ft³ ((192 kg/m³)), the processincludes the additional steps of:

[0030] (1) the addition of expendable carbon fibers in the castingprocess and/or other temporary support material; and

[0031] (2) firing the billet at about 1300° F. to remove the carbonfibers or other support material prior to the final firing atapproximately 1600° F. or above.

[0032] When the dispersed silica fibers and dispersed alumina fibers arecombined, the pH may be acidic, and if so, should be adjusted to neutralwith ammonium hydroxide. The slurry should contain about 12 to about 25parts water to about 1 part fiber. The slurry is mixed to a uniformconsistency in a V-blender in 5 to 20 minutes. The boron nitride can beadded at this point (2.85% by weight of the fibers) and mixed to auniform consistency in a V-blender for an additional 5 to 15 minutescreating a Master Slurry. The preferred mixing procedure uses 15 partswater to 1 part fiber and the slurry is produced in about 20 minutes ofmixing. At lower density formulations, expendable carbon fibers are usedto give “green” strength to the billet prior to the final sintering. Thepercent of carbon fiber used varies greatly depending on the diameter,length and source of the fiber and the ultimate density of the materialbeing produced. The percent of carbon fiber per dry weight of materialshould range between 1% and 10%. The source of the carbon fiber can takemany forms including nylon, cellulose, and purified graphite basedcarbon in fibrous form. Carbon fibers added in the casting process areeliminated by firing the billets at 1350° F. prior to the final firingat 2450° F.

[0033] The Master Slurry is poured into a mold for pressing into thedesired shape. The water is withdrawn rapidly and the resulting felt iscompressed at 10 to 20 psi. Rapid removal of the water is required toprevent the fibers from separating. If graded properties are desired inthe resultant material, the slurry can be allowed to settle and thefibers to partially separate before the removal of the water.

[0034] The final density of the finished restorative material isdetermined in part by the amount of compression placed on the felt,varying the wet molded dimension in relation to the fiber content. Theformulation of the present invention has been prepared in densitiesranging from about 0.05 to 0.48 g/cc. It can, however, be prepared inlower and higher densities.

[0035] After molding, the restorative material can be dried and fired bythe following procedure. The material is first dried in an oven for 18hours; the temperature, initially 38° C., is raised at a rate of 11° C.per hour to 104° C., held there for 4 hours, raised again at a rate of11° C. per hour to 150° C., and held there for 4 hours. The material istaken directly from the drying oven, placed in the firing furnace, andfired. A temperature rise rate of 220° C. per hour or less is requiredin order to avoid cracking and warping in the case of a 15 cm×15 cm×7.5cm block of material. For larger blocks, slower heating rates may berequired. The maximum firing temperature may vary from 1200° C. to 1600°C. depending upon the fiber ratio used, amount of boron nitride, and thefinal density of the material that is desired.

[0036] The temperature rise rate is chosen to permit relatively uniformtemperatures to be achieved throughout the material during the process.A faster temperature rise rate causes non-uniform temperatures to beachieved throughout the material during the process. A fastertemperature rise rate causes nonuniform strength and density and maycause cracking. Longer or higher temperature firing results in highershrinkage and related greater resistance to subsequent shrinkage, aswell as a shorter lifetime to devitrification under cyclic exposures tohigh temperatures. The maximum firing temperature is dependent upon thefiber ratio used and the density of the composite desired. The firingtime and maximum temperature are selected to allow sufficient shrinkageto achieve stabilization and fiber fusion while not allowing anydevitrification. After firing, the material may be machined to obtainany desired final dimensions.

[0037] The following method of preparing the porous material, andseveral proposed uses, was described in U.S. Pat. No. 5,629,186.

[0038] Preparing the Matrix

[0039] In general, the method includes forming a fiber slurry havingdesired viscosity and fiber dispersion characteristics, allowing theslurry to settle under conditions that produce a selected fiber densityand orientation, drying the resulting fiber block, and sintering theblock to form the desired fused-fiber matrix.

[0040] A. Fiber Treatment

[0041] The silica (SiO₂) and/or alumina (Al₂O₃) fibers used in preparingthe matrix are available from a number of commercial sources, inselected diameters (fiber thicknesses) between about 0.5 μm-20 μm. Apreferred silica fiber is a high purity, amorphous silica fiber (99.7%pure), such as fabricated by Manville Corporation (Denver, Colo.) andsold under the fiber designation of “Q-fiber”. High purity aluminafibers (average 3 microns) may be procured, for example, from ICIAmericas, Inc. (Wilmington, Del.).

[0042] In a preferred heat treatment, the silica fibers are compressedinto panels, e.g., using a Torit Exhaust System and compaction unit. Thecompressed panels are sent passed through a furnace, e.g., a HarperFuzzbelt furnace or equivalent at 2200° F. for 120 minutes,corresponding to a speed setting of about 2.7 inches/minute. The heattreatment is used to close up surface imperfections on the fibersurfaces, making the matrix more stable to thermal changes on sintering.The heat treatment also improves fiber chopping properties, reducingfabrication time.

[0043] In a preferred method, the heat-treated fibers are washed toremove debris and loose particles formed during fiber manufacturing.

[0044] B. Preparing a Fiber Slurry

[0045] Silica and/or alumina fibers from above are blended to form afiber slurry that is used in forming a “green-state” block that can besintered to form the desired matrix.

[0046] The slurry is formed to contain, in an aqueous medium, silica,alumina, or silica and alumina fibers of the type described above, at afiber:liquid weight ratio of between about 1:25 to 1:70, where theliquid weight refers to the liquid weight of the final slurrypreparation.

[0047] The slurry preferably includes a thickening agent effective togive the slurry a viscosity between about 1,000 and 25,000 centipoise,as measured by standard methods. The viscosity agent may be any of anumber of well-known hydrophilic polymers, such as polyvinylalcohol,polyvinylacetate, polyvinylpyrrolidone, polyurethane, polyacrylamide,food thickeners, such as gum arabic, acacia, and guar gum, andmethacrylate type polymers. The polymers preferably have molecularweights greater than about 25-50 Kdaltons, and are effective to increasesolution viscosity significantly at concentrations typically betweenabout 0.5-10 weight percent solution.

[0048] Preferred thickening agents polymers that also have tacky oradhesive properties, such as methyl cellulose, terpolymers of maleicanhydride, alkyl vinyl ether, and an olefin (U.S. Pat. No. 5,034,486),copolymers of ethylene and olefins (U.S. Pat. No. 4,840,739),cellulose-containing pastes (U.S. Pat. No. 4,764,548), and soypolysaccharides. One preferred thickening agent is methylcellulose,e.g., the polymer sold under the tradename Methocel A4M and availablefrom Dow Chemical Co. (Midland, Mich.).

[0049] Where the matrix is formed of high-purity silica fibers and/oralumina, the slurry is also formed to contain a source of boron thatfunctions, during sintering, to form a boron/silica or boron/aluminasurface eutectic that acts to lower the melting temperature of thefibers, at their surfaces, to promote fiber/fiber fusion at the fiberintersections. In a preferred embodiment, the boron is supplied in theslurry as boron nitride particles 15 to 60 μm in size particles. Suchparticles can be obtained from Carborundum (Amherst, N.Y.). The amountof boron nitride is preferably present in the slurry in an amountconstituting between about 2-12 weight percent of the total fiberweight.

[0050] The adhesive property of the thickening agent described above isuseful in adhering particles of boron nitride and, if used, siliconcarbide, to the fibers in the slurry, to produce a relatively uniform ofparticles in the slurry, and prevent the particles from settling out ofslurry during the molding process described below.

[0051] The slurry preferably also contains a dispersant which acts tocoat the fibers and help disperse the fibers, both to increase slurryviscosity, and to prevent silica fibers from “bundling” and settling outof the slurry as fiber aggregates during the molding process describedbelow. The dispersant is preferably one which imparts a significantcharge and/or hydrophilicity to the fibers, to keep the fibers separatedduring slurry formation and settling during the molding process.

[0052] For use with silica fibers, ammonium salts are particularlyuseful as dispersants, because the ammonium cation is released from thematrix in the form of ammonia during matrix drying and/or sintering.Preferred ammonium salts are the salts of polyanionic polymers, such asammonium polymethylmethacrylate, or the ammonium salt of othercarboxylated polymers. One preferred dispersant agent is the ammoniumpolymethylmethacrylate polymer sold by R. T. Vanderbilt under thetradename Darvan 821A. The polymer dispersant is preferably added to theslurry to make up between about 0.2 to 5 percent of the total liquidvolume of the slurry.

[0053] The slurry may further contain between about 1-5 percent byweight silicon carbide particles, such as obtainable from WashingtonMills Electro Minerals Corp. (Niagara Fall, N.Y.).

[0054] A preferred method for preparing a slurry of the type justdescribed is detailed as follows. Briefly, heat-treated silica fibersare suspended in water at a preferred fiber:water ratio of about 1:300to 1:800. The fiber slurry is pumped through a centrifugal cyclone toremove shot glass and other contaminants, such as high soda particles.The fiber cake formed by centrifugation is cut into segments, dried at550° F. for at least 8 hours, and then broken into smaller chunks forforming the matrix.

[0055] Fragments of the silica fiber cake are mixed in a desired weightratio with alumina fibers, and the fibers are dispersed in an aqueoussolution containing the dispersing agent. At this point, the fibers arepreferably chopped to a desired average fiber length in alow-shear/high-shear mixer. In general, the greater the degree ofchopping, the shorter the fibers, producing better packing and a lessopen matrix structure. Similarly, longer fibers lead to more open matrixstructure. The fiber mixing is preferably carried out under condition toproduce average fiber sizes of a selected size in the 1-10 mmfiber-length range.

[0056] After mixing, the fibers are allowed to settle, and theliquid/fiber ratio is reduced by decanting off some of the dispersingliquid. To this slurry is added an aqueous gel mixture formed of theviscosity agent, e.g., methyl cellulose, and the matrix particles, e.g.,boron nitride particles, and the slurry components are mixed to form thedesired high-viscosity slurry. The slurry is now ready to be transferredto a casting mold, to prepare the green-state block, as described in thenext section.

[0057] C. Forming a Dried Fiber Block

[0058] According to an important aspect of the method, the slurry isallowed to settle and is dewatered in a fashion designed to achieve arelatively uniform fiber density throughout the matrix, and relativelyrandomly oriented fibers, i.e., with little a fiber orientationpreference in the direction of settling.

[0059] In the first step, a slurry is added to a mold equipped with alower screen sized to retain slurry fibers. For fiber sizes in the range1-10 mm, the screen has a mesh size between about 8 to 20 squares/inch.The mold has a lower collection trough equipped with a drain and avacuum port connected to a suitable vacuum source.

[0060] Initially, the slurry is added to the mold and, after stirringthe slurry to release gas bubbles, is allowed to settled under gravity,until the level of water in the mold is about 1-2 inches above the levelof the desired final compaction height, i.e., the final height of thedewatered block. For a slurry of about 12 l added to a 18 cm² squaremold, the initial settling takes about 3-10 minutes.

[0061] The partially drained slurry in the mold is now compacted with acompacting ram to force additional water from slurry. This is done byallowing the ram to act against the upper surface of the slurry underthe force of gravity, while draining the water forced through a screenfrom the mold. Water is squeezed from the slurry until the ram reachesthe desired compaction height. With the slurry volume and molddimensions just given, a ram having a weight of about 7 lbs is effectiveto compress the partially dewatered slurry in a period of about 0.2 to 2minutes.

[0062] In the final step of compacting and dewatering, the drain isclosed and vacuum is applied to a port until the block is completelydewatered. A vacuum of between about 0.01 to 0.5 atm is effective toproduce complete dewatering of the mold in a period of about 0.2 to 5minutes. The vacuum dewatering may result in the upper surface of theblock pulling away from the ram.

[0063] The dewatered block is now removed from the mold and dried in anoven, typically at a temperature between 250° F.-500° F. In the driedmatrix, the viscosity agent, and to a lesser extent, the dispersantagent, act to bond the fibers at their intersections, forming a rigid,non-fused block. The target density of the matrix after drying isbetween about 3.3 to 5.3 pounds/ft³.

[0064] The green-state matrix may be formed to include sacrificialfiller element(s) that will be vaporized during sintering, leavingdesired voids in the final fused matrix block. The filler elements arepreferably formed of polymer or graphite. An array of parallel rods maybe placed in the mold, at the time the slurry is added. Slurry settlingand dewatering are as described above, to form the desired green-stateblock with the included sacrificial element.

[0065] The first step is the slurry formation. The slurry may be asingle fiber suspension containing a desired size range and fibercomposition. Alternatively, for forming a discontinuous or step fibermatrix, two or more slurries having different fiber thicknesses,densities, and/or fiber compositions may be formed.

[0066] After the slurry is introduced into the mold, the steps insettling and dewatering the slurry can be varied to produce either acontinuous gradient of fiber density or a uniform fiber density. Thesteps in forming a uniform gradient, including an initial settling step,followed by ram compaction and final dewatering by vacuum have beenconsidered above.

[0067] To produce a continuous gradient of fiber densities, the slurryis first subjected by dewatering by vacuum, causing material closest tothe screen to be compacted preferentially. When a desired gradient isachieved, the slurry is gravity drained to dewater the slurry, thenram-compacted for further dewatering. The slurry may be subjected to afinal vacuum dewatering.

[0068] To produce a block having a series of discontinuous layers, eachwith a uniform fiber density, each successive slurry is handledsubstantially as described above for the uniform-density block. Thelayers can be formed by successively casting layer upon layer in themold, with each successive layer being compacted as described above.Alternatively, a series of block layers, each with a distinctive fibersize/composition and/or density is prepared. Before drying, theindividual blocks are placed together in layers, to form the desireddiscontinuous-layer block. The layers may be “glued” together beforedrying by applying, for example, a layer of boron nitride in theviscosity agent between the layers.

[0069] D. Fused Fiber Matrix

[0070] In the final step of matrix formation, the green-state block fromabove is sintered under conditions effective to produce surface meltingand fiber/fiber fusion at the fiber crossings. The sintering is carriedout typically by placing the green-state block on a prewarmed kiln car.The matrix is then heated to progressively higher temperature, typicallyreaching at least 2,000° F., and preferably between about 2,200°F.-2,400° F., until a desired fusion and density are achieved, thetarget density being between 3.5 and 5.5 pounds/ft³. For a block formedsolely of alumina fibers, a maximum temperature of about 2,350° F. issuitable.

[0071] In a preferred method, discussed above, the matrix is formed withhigh-purity silica fibers that contain little or no contaminating boronand/or with alumina fibers that are also substantially free of boron. Inorder to achieve fiber softening and fusion above 2,000° F., typicallyin the temperature range 2,000° F.-2,200° F., it is necessary tointroduce boron into the matrix during the sintering process, to form asilica/boron or alumina/boron eutectic mixture at the fiber surface.Boron is preferably introduced, as detailed above, by including boronnitride particles in the green-state block, where the particles areevenly distributed through the block.

[0072] During sintering, the boron particles are converted to gaseous N₂and boron, with the released boron diffusing into the surface of theheated fibers to produce the desired surface eutectic, and fiber fusion.The distribution of boron particles within the heated block ensures arelatively uniform concentration of boron throughout the matrix, andthus uniform fusion properties throughout.

[0073] Also during fusion, the viscosity agent and dispersant agentsused in preparing the green-state block are combusted and driven fromthe block, leaving only the fiber components, and, if added, siliconcarbide particles.

[0074] Where the green-state block has been constructed to include asacrificial element, the sintering is also effective to vaporize thiselement, leaving desired voids in the matrix, such as a lattice ofchannels throughout the block.

[0075] After formation of the fused-fiber matrix, the matrix block maybe machined to produce the desired shape and configuration. For example,the matrix can be formed by drilling an array of channels in the block;or by cutting the block into thin plates.

[0076] Polymer Fiber Matrix

[0077] In another aspect, the invention includes a fibrous polymermatrix. The matrix is composed of fused polymer fibers, and ischaracterized, in dry form, by: (a) a rigid, three-dimensionallycontinuous network of open, intercommunicating voids, and (b) a freevolume of between about 90-98 volume percent. The fibers may alsoinclude up to 80 percent by weight of either silica fibers, aluminafibers, or a combination of the two fibers types.

[0078] The matrix is designed for use particularly as a substrate forcell growth in vitro, and as such, contains an array of channelsextending through the matrix. In an alternative embodiment, the matrixhas a multi-plate configuration.

[0079] The fused polymer matrix is formed substantially as described forthe silica, alumina, or silica/alumina fiber matrices described above,but with the modifications now to be discussed.

[0080] The polymer fibers used in constructing the matrix may be anythermoplastic polymers that can be heat fused, typically when heated inthe range 400° F.-800° F. Exemplary polymer fibers include polyimide,polyurethane, polyethylene, polypropylene, polyether urethane,polyacrylate, polysulfone, polypropylene, polyetheretherketone,polyethyleneterphthalate, polystyrene, and polymer coated carbon fibers.Fibers formed of these polymers, and preferably having thickness in the0.5 to 20 μm range, can be obtained from commercial sources. The fibersmay be chopped, i.e., by shearing, to desired lengths, e.g., in the 0.1to 2 mm range, by subjecting a suspension of the fibers to shear in ahigh-shear blender, as described above.

[0081] The polymer fibers may be blended with up to 80 weight percentsilica and/or alumina fibers of the type described above. Preferably,the silica fibers are heat treated to close up surface imperfections onthe fiber surfaces, as described above. The alumina fibers may also beheat treated, e.g., under the sintering conditions described above, toproduce surface granulation on the fiber.

[0082] The aqueous fiber slurry used in preparing the matrix contains,in addition to fibers, a viscosity agent effective to produce a finalslurry viscosity between about 1,000 and 25,000 centipoise. Viscosityagents of the type mentioned above are suitable. If the polymers fibersare relatively hydrophobic, or if the fibers include silica fibers, theslurry should contain a dispersant effective to prevent the fibers fromaggregating on settling. Such a dispersant may include surfactantsand/or charged polymers, and/or block copolymers, such aspolyethylene/polypropylene block copolymers known to enhance thehydrophilicity of polymer surfaces.

[0083] The slurry also contains an adhesive agent effect to retain thegreen-state fiber network in a rigid condition once it is formed. Eitherthe viscosity agent or dispersant may supply the necessary adhesiveproperties. Alternatively, a separate adhesive component may be added tothe slurry.

[0084] The above slurry is placed in a settling mold, as above, and thefibers are allowed to settle under dewatering conditions, substantiallyas described above, to yield randomly oriented fibers having a desiredfiber density. The network is formed into a greenstate block by drying,e.g., at 100° F.-300° F.

[0085] In the final step, the greenstate block is heated underconditions, typically at a temperature between 400° F.-800° F.,effective to produce fiber fusion at the fiber points of intersection.The selected temperature is near the softening point of thethermoplastic polymer. At this temperature, the polymer fibers fuse withone another and with silica and/or alumina fibers in the block toproduce the desired rigid, fused fiber matrix.

[0086] Utility: Cell-Growth Substrate

[0087] The low-density matrix described above in the above sections isdesigned particularly for use as a substrate for cell growth in vitro,or in vivo as an implantable substrate.

[0088] The architecture of the matrix, and particularly thecharacteristics of a rigid, three-dimensionally continuous network ofopen, intercommunicating voids, and a free volume of between about 90-98volume percent, permit rapid cell growth in three dimensions.

[0089] In a preferred embodiment, the matrix is formed of silica fibers,typically in an amount between about 50-100 weight percent of the totalfiber weight. In another preferred embodiment, the matrix is formed toinclude alumina fibers, preferably heated to produce surfacegranulation, in an amount of fiber preferably between about 20-80 weightpercent fiber.

[0090] The silica and/or alumina fibers may enhance cell adhesion,and/or adhesion of growth factors, such as fibrofectin, vibronectin, orfibrinogen. Representative cell culture and cell implantationapplications are discussed below.

[0091] A. Cell Culture

[0092] In one general embodiment, the matrix of the invention is used tosupport cell growth in a cell culture system in vitro. A firstconfiguration uses a fiber matrix having a lattice of channels extendingthrough the matrix. The matrix is supported in a culture vesselpartially filled with culture medium. The medium is pumped into andthrough the matrix. The system further includes a filter placed in-linewith the pump for extracting desired cell products and/or purifying themedium of cell bi-products. Suitable heating and gas-supply means formaintaining desired gas and temperature control of the medium may alsobe employed, as well as means for replenishing the medium. A second cellculture configuration utilizes a multi-plate matrix. The plates in thematrix are submerged in a suitable cell culture medium in a vessel, andthe medium is circulated, through the plates by a pump. Theconfiguration may also include a filter and culture control means, asindicated above.

[0093] In a third configuration, the matrix is present as fragmentswhich are suspended in a culture medium. The matrix fragments areproduced preferably by fragmentizing matrix plates of having a thicknessbetween about 0.2 to 2 mm. The matrix fragments, being slightly denserthan the culture medium, can be maintained in a suspended state, bygentle stirring or gas bubbling, and can be separated readily from themedium by settling, centrifugation or filtration.

[0094] It will be understood that the matrix in the configurations isfirst sterilized, conventionally, and may be further treated topreabsorb agents which promote cell adhesion to the substrate. Typicallythese agents include a divalent cation, such as Mg⁺², and a glycoproteinsuch as fibronectin, polyethylene, and/or fibrinogen. The pretreatmentpreferably involves incubating the sterilized matrix in a serum or othermedium containing the growth factors of interest.

[0095] Alternatively, the fibers, meaning either silica or polymerfibers, may be derivatized by covalent attachment of desired growthfactors, such as bone osteogenic factor, cytokines, or the like. Methodsfor derivatizing the free hydroxyl groups on silica fibers, or freehydroxyl, amine, carboxyl, suldydryl, or aldehyde groups that may bepresent on polymer fibers are well known.

[0096] B. Implantable Cell Matrix

[0097] In another general application, the matrix of the invention isused as an implantable substrate for supporting cell growth in vivo. Asone example of this application, a hip replacement device having a stemdesigned to be inserted and locked into the femur of subject, and a ballwhich will serve as the ball of the repaired hip joint. The stem has atitanium inner core which is formed integrally with the ball. The coveris ensheathed in a fused-fiber matrix constructed according to theinvention, and which forms a covering over the core. The matrix coveringis preferably formed by machining a fused-fiber block of the typedescribed above. The covering may be attached to the stem core by asuitable adhesive, or by heat fusion near the melt temperature of thetitanium, in the case of a silica and/or alumina fiber matrix.

[0098] In operation, the matrix on the stem provides a substrate for thegrowth and infusion of osteoblast cells, acting to weld the stem to thebone through a biological bone structure. The matrix fibers may includebone growth factors for promoting bone cell growth into the matrix.

[0099] An implantable cell substrate device can be constructed accordingto the invention. The device is designed for use as an implantablesubstrate for supporting growth of a selected tissue cells, such aspancreatic cells or fibroblasts, capable of producing desired cellmetabolites such as insulin or interferon.

[0100] This device has a tubular construction, and provides a spiraledinner core for supporting cell growth, while allowing body fluids tobathe the cells, bringing nutrients and removing cell products. Thedevice is formed preferably by machining a block of fused-fiber matrixof the type disclosed herein. The outer surface of the device is coatedwith a biocompatible material, such as silicon rubber to insulate thefiber matrix from direct contact with the surrounding tissue.

[0101] In operation, the device is seeded with the desired cells inculture, preferably until the spiraled core has a maximum cell density.The device is then implanted into a desired tissue region, e.g., anintramuscular site.

[0102] The two examples described above illustrate two of a variety ofimplant devices, for bone repair, bone replacement, and tissue-cellaugmentation or replacement that may be prepared using thecell-substrate matrix material of the invention.

[0103] Utility: Chromatography

[0104] The silica-fiber matrix of the invention is also useful forchemical and cell chromatographic separations.

[0105] In one embodiment, the matrix can serve as a substrate forthin-layer chromatographic separations, using well-known solvent-systemsand development conditions. The matrix in this application is preferablya thin matrix plate, formed, for example, by slicing a matrix block to adesired thickness, e.g., between 1-3 mm. Alternatively, thin plates maybe prepared by slurry settling, as described above, in thin-plate molds.

[0106] In a related aspect, the matrix serves the role of a silica gelcolumn for chemical separations by silica gel chromatography. As above,the matrix may be machined from a block matrix mold, or formed bysettling in a suitable cylindrical mold. For both applications, thedensity of the matrix is preferably above the 3.5-5.5 pounds/ft³ matrixdensity that is employed for cell culture.

[0107] According to another aspect of the invention, the fused-fibermatrix material having a density between about 3.5 and 5.5 pounds/ft³ isuseful for cell-separation chromatography, and typically for use inseparating cells and other particles above about 1 micron in size fromserum components in a blood sample.

[0108] A diagnostic test strip can be prepared for use in detecting aserum components, such as glucose, cholesterol, or acholesterol-containing lipoprotein, such as low density lipoprotein orhigh-density lipoprotein particles. The strip, which is formed of thefused-silica fiber matrix material of the invention, includes anapplication site at one strip end a detection site at the opposite end.The detection site may include reagents for producing a detectable colorsignal in the presence of a selected serum analyte. Alternatively, serumfrom this site may be transferred by physical contact to a separatereagent pad.

[0109] In operation, a blood sample, e.g., a 25-200μ sample, is added tothe application site, and the sample is drawn by capillarity toward thestrip's opposite end. Migration of the sample through the interstices ofthe matrix acts to retard the migration rate of larger particles,including blood cells, causing separation of the blood cells separatedinto a slower migrating blood cell fraction and a faster-migrating serumfraction, which is received at the detection site free of blood cells.Analyte detection may occur at this site, or a separate detection padmay be brought in contact with the strip site, to draw serum into thepad.

[0110] Methods of use

[0111] Drugs or other biologically active materials can be incorporatedinto the materials, making the materials a drug delivery device. Thedevice can be implanted into an animal. The density of the material andthe loading of the drug can be altered in order to modulate the timerelease property of the device. The drug can be a small moleculeorganic, a protein, a peptide, a nucleic acid, a growth factor, or anyother biologically active substance.

[0112] The materials can be used as a filler material. Filler materialscan be used to reinforce organic, inorganic, or metallic materials. Thefiller materials can be used to reinforce polymers. The materials can beused as a composite filler for collagen.

[0113] All of the compositions and/or methods disclosed and claimedherein can be made and executed without undue experimentation in lightof the present disclosure. While the compositions and methods of thisinvention have been described in terms of preferred embodiments, it willbe apparent to those of skill in the art that variations may be appliedto the compositions and/or methods and in the steps or in the sequenceof steps of the methods described herein without departing from theconcept, spirit and scope of the invention. More specifically, it willbe apparent that certain agents which are both chemically andphysiologically related may be substituted for the agents describedherein while the same or similar results would be achieved. All suchsimilar substitutes and modifications apparent to those skilled in theart are deemed to be within the spirit, scope and concept of theinvention.

What is claimed is:
 1. A porous composition comprising: up to about 100%by weight silica; and up to about 60% by weight alumina; wherein thecomposition has a density of at least about 6 pounds per cubic foot(96.1 kg/m³).
 2. The composition of claim 1 , wherein the silicacomprises up to about 50% by weight cristobalite.
 3. The composition ofclaim 1 , further comprising an additional metal oxide.
 4. Thecomposition of claim 1 , further comprising tantalum oxide or zirconiumoxide.
 5. The composition of claim 1 , further comprising carbon fiber.6. The composition of claim 1 , further comprising a drug.
 7. Thecomposition of claim 1 , further comprising silica gel.
 8. Thecomposition of claim 1 , wherein the density is at least about 8 poundsper cubic foot (128 kg/m³).
 9. The composition of claim 1 , wherein thedensity is at least about 12 pounds per cubic foot (192 kg/m³).
 10. Thecomposition of claim 1 , wherein the density is at least about 36 poundsper cubic foot (577 kg/m³).
 11. The composition of claim 1 , wherein thedensity is at least about 64 pounds per cubic foot (1025 kg/m³).
 12. Thecomposition of claim 1 , wherein the mean pore diameter of thecomposition is up to about 5 microns.
 13. The composition of claim 1 ,wherein the mean pore diameter of the composition is at least about 5microns.
 14. The composition of claim 1 , wherein the mean pore diameterof the composition is at least about 50 microns.
 15. The composition ofclaim 1 , wherein the mean pore diameter of the composition is at leastabout 100 microns.
 16. The composition of claim 1 , wherein the meanpore diameter of the composition is about 0.1 micron and about 1 micron.17. The composition of claim 1 , wherein the mean pore diameter of thecomposition is about 5 microns to about 10 microns.
 18. The compositionof claim 1 , wherein the mean pore diameter of the composition is about20 microns to about 50 microns.
 19. The composition of claim 1 , whereinthe mean pore diameter of the composition is about 100 microns to about400 microns.
 20. The composition of claim 1 , wherein the surfaceproperties of the composition has been modified by a chemical reaction.21. The composition of claim 1 , wherein the surface properties of thecomposition has been modified by a chemical reaction to increase thehydrophilicity.
 22. The composition of claim 1 , wherein the surfaceproperties of the composition has been modified by a chemical reactionto increase the hydrophobicity.
 23. The composition of claim 1 , whereinthe exposed surface is at least about 50% silicon dioxide.
 24. Thecomposition of claim 1 , wherein the exposed surface is at least about75% silicon dioxide.
 25. The composition of claim 1 , wherein theexposed surface is at least about 95% silicon dioxide.
 26. A porouscomposition prepared from a composition comprising: about 1% to about50% by weight alumina; about 50% to about 98% by weight silica; andabout 1% to about 5% by weight boron.